Latest Review Date: October 2024

POLICY:

Measurement of serum tumor marker CA 15-3 (CA 27.29) for monitoring patients with known breast cancer may be considered medically necessary.

Measurement of serum tumor marker CA 15-3 (CA 27.29) when used as a diagnostic or screening test for breast cancer is considered investigational.

Measurement of serum tumor marker CA 19-9 for monitoring patients with known pancreatic or biliary cancer (i.e., gallbladder, intrahepatic biliary and extrahepatic biliary) may be considered medically necessary.

Measurement of serum tumor marker CA 19-9 when used as a technique to screen, diagnose, determine prognosis, assess response to therapy, or monitor for recurrence of gastrointestinal malignancies* (except as indicated above) is considered investigational. 

Measurements of serum tumor marker CA 72-4 when used as a technique to screen, diagnose, determine prognosis, assess response to therapy, or monitor for recurrence of gastrointestinal malignancies* is considered investigational.

*Gastrointestinal malignancies include cancers associated with the esophagus, stomach, small intestine, appendix, colon, rectum, anus, liver, biliary tract and pancreas.

DESCRIPTION OF PROCEDURE OR SERVICE:

Serum tumor markers are substances produced by cells in response to cancer or certain noncancerous conditions. Most tumor markers are made by normal cells as well as cancer cells; however, they are produced at much higher levels in cancerous conditions. Serum tumor markers have been investigated in many malignancies, including most prominently myeloma, germ cell tumors, and prostate cancer. This policy focuses on specific tumor markers for breast and gastrointestinal malignancies.

For breast cancer, the most extensively investigated serum tumor markers besides HER2 are those associated with the MUC-1 gene. For gastrointestinal cancer (including gastric, pancreatic, and colorectal cancer) the most extensively studied tumor markers, other than CEA, are those related to mucinous glycoproteins. The MUC-1 gene encodes a cell-associated mucin-like antigen, and different antibodies may be used to detect different epitopes. CA 15-3 and CA 27.29 are two related monoclonal antibodies that detect epitopes encoded by the MUC-1 gene. While much of the literature has focused on the use of CA 15-3, it has been largely replaced by CA 27.29, which is reportedly more sensitive. The mucinous glycoproteins of the gastrointestinal tract include CA 19-9, and CA 72-4, depending on which antibody is used.

Since serum tumor markers can also be detected in normal or benign lesions, significantly elevated circulating levels may occur with malignancy by one or more of the following mechanisms: (1) overexpression of the antigen by malignant cells; (2) a large tumor burden; and/or (3) slower clearance of the marker. For example, since most tumor markers are cleared by the liver, liver abnormalities (whether benign, malignant, or inflammatory) may elevate tumor marker concentrations due to impaired clearance. Because most tumor markers are not unique to malignancy, cut-off points must be established for normal versus abnormal marker levels. In contrast, serial monitoring of serum tumor markers in a setting of established malignancy may not require such cutoff points. Various clinical applications of serum tumor markers can be broadly divided into two categories, those involving a single measurement and those involving serial measurements.

The CA 15-3/CA 27.29 tumor marker is associated with breast cancer and is useful in assessing whether treatment is working or if cancer has recurred. The CA 27.29 tumor marker alone can be used to detect cancer metastasis or recurrence.

The CA 19-9 marker is associated with cancers of the colon, stomach, and bile duct. Elevated levels of CA 19-9 may indicate advanced cancer in the pancreas, but it is also associated with noncancerous conditions, including gallstones, pancreatitis, cirrhosis of the liver, and cholecystitis. This tumor marker can be useful in assessing whether treatment is working.

The CA-72-4 marker testing is most commonly used for the diagnosis and management of gastrointestinal cancers. It has also been studied for use in gynecological cancers.

*This policy does not address serum tumor markers for bladder cancer

KEY POINTS:

This policy was created in 2004 with the most recent literature review performed on October 29, 2024.

Summary of Evidence

CA 15-3 has been investigated for use in the management of patients with breast cancer. Its low detection rate in early stage disease indicates that CA 15-3 cannot be used to screen or diagnose patients. It has been widely used to monitor the effectiveness of treatment for metastatic cancer. Elevated serum CA 15-3 concentrations have been found in five percent of stage I, 29 percent of stage II, 32 percent of stage III and 95 percent of stage IV carcinomas of the breast. Most (96 percent) patients with a CA 15-3 increase of greater than 25 percent have disease progression. Most (nearly 100 percent) patients with a CA 15-3 decrease of greater than 50 percent are responding to treatment. The evidence is insufficient to determine that the use of tumor marker CA 15-3 for diagnosis or screening of breast cancer results in an improvement in the net health outcomes. Serial measurements of CA 15-3 in following the course of treatment in women diagnosed with breast cancer, especially advanced metastatic breast cancer, has been shown to adequately suggest treatment failure, therefore, the evidence is sufficient to determine that the use of tumor marker CA 15-3 in the monitoring of patients with breast cancer results in an improvement in the net health outcomes.

CA 19-9 has most notably been investigated for use in pancreatic cancer patients. Reports are mixed regarding outcomes when used in pre and postoperative determinations, and in monitoring patients receiving chemotherapy or radiotherapy. The specificity and sensitivity of CA 19-9 is inadequate for reliable diagnosis of pancreatic cancer when used alone. High levels of CA 19-9 are increased in biliary disease due to the enhanced production of CA 19-9 from the biliary epithelial cells. Extreme increases in CA 19-9 levels can lead to a misdiagnosis of pancreatic or biliary malignancy. CA 19-9 should never be considered the gold standard for diagnosis. The evidence is insufficient to determine that the use of tumor marker CA 19-9 for the diagnosis of patients with GI cancer results in an improvement in the net health outcomes.

There exists limited evidence that suggesting the use of CA 19-9 for monitoring of patients with GI cancers is beneficial to providing information regarding the progression of disease and has practical value in the management of GI cancers. Recruitment for large scale studies is challenging, but this technology is believed to be of value. CA 19-9 is considered to have sufficient evidence to determine that the use of tumor marker for the monitoring of patients with GI cancer results in an improvement in the net health outcomes.

A small prospective study has been identified investigating the use of CA 72-4 in various metastatic cancers. Positivity rates of CA 72-4 vary based on different assay cut-off levels. There is a paucity of well-designed studies that convincingly proves the use of CA 72-4 results in an improvement in the net health outcomes as a technique to diagnose, determine prognosis, select therapy, assess response to therapy, or monitor for recurrence of either breast or gastrointestinal malignancies. The evidence is insufficient to determine that the use of CA 72-4 results in an improvement in the net health outcomes.

Controlled studies showing the clinical utility of the serum tumor markers addressed in this policy and improved health outcomes in patients with breast, pancreatic, gastric, or colon cancer are lacking. In terms of monitoring response to therapy of metastatic disease, the serial measurement of serum tumor markers correlates well with clinical response criteria. Of concern is the lack of valid criteria for interpreting changes in marker levels. Criteria have been suggested, but these have not been universally accepted. The evidence is insufficient to determine that the use of tumor markers for monitoring response to therapy results in an improvement in the net health outcomes.

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN)

The NCCN task force guidelines recommend that tumor markers be classified by indication as diagnostic, prognostic, predictive and companion tests. An individual marker may serve more than one purpose and thus can fall into more than one category of biomarker.

CA 15-3 and 27.29:

• NCCN Breast Cancer V.4.2023 recommends use of CA 15-3 and 27.29 as part of findings for identification of disease progression. An isolated increase in tumor marker should not be used as the only indicator of disease progression as these two biomarkers may also increase if metastatic disease is responding to treatment.

CA 19-9:

• NCCN Pancreatic Adenocarcinoma V.2.2023 recommends use of CA 19-9 as Pancreatic adenocarcinoma pre-op workup, post treatment, and surveillance, differential diagnosis, screening, staging, determining resectability, et al. Levels may be elevated up to 2 years before pancreatic CA diagnosis.
• NCCN Small Bowel Adenocarcinoma Version 1.2023 recommends use of CA 19-9 as Workup and surveillance for small bowel adenocarcinoma
• NCCN Hepatobiliary Cancers Version 1.2023 recommends use of CA 19-9 as Gallbladder cancer workup (on findings such as jaundice or a mass found on imaging) and surveillance. CA 19-9 is a baseline test and should not be done to confirm diagnosis. Consider baseline CA 19-9 after biliary decompression; Intrahepatic (such as isolated intrahepatic mass) and extrahepatic cholangiocarcinoma workup. CA 19-9 is a baseline test and should not be done to confirm diagnosis
• NCCN Ovarian Cancer Version 2.2023 recommends use of CA 19-9 as May be clinically indicated in the workup and management of epithelial ovarian, fallopian tube, primary peritoneal, and less common ovarian cancers

American Society of Clinical Oncology (ASCO)

The most recent update to the ASCO recommendations for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of breast cancer occurred in 2007.

Table 1. ASCO Guidelines for the Use of Tumor Markers in Breast Cancer

ASCO expanded the scope of the guidelines for use of tumor markers in gastrointestinal cancer to include CA 19-9 as a marker for pancreatic cancer in 2006. The recommendations for evaluation of CA 19-9 levels are as follows:

• CA 19-9 is least sensitive for small, early-stage pancreatic carcinomas and thus is not effective for the early detection of pancreatic cancer or as a screening tool
• Use of CA 19-9 levels alone is not recommended for use in determining operability
• Rising levels of CA 19-9 postoperatively may predict recurrent disease, but confirmation with imaging studies and/or biopsy is required.
• CA 19-9 can be measured at the start of treatment for locally advanced metastatic disease and every 1-3 months during active treatment; elevation of levels in serial determinations may be an indication of progressive disease, but confirmation with other studies is required
• 5-10% of patients lack the enzyme necessary to produce CA 19-9; in these patients with low or absent titer of CA 19-9, monitoring disease with this tumor marker will not be possible

U.S. Preventative Services Task Force Recommendations

Not applicable.

KEY WORDS:

Serum tumor markers, CA 19-9, CA 72-4, CA 15-3, CA 27.29, pancreatic cancer, biliary cancer, breast cancer, GI malignancies, gastrointestinal malignancies, gastrointestinal cancer, GI cancer, gallbladder cancer, intrahepatic biliary cancer, extrahepatic biliary cancer, esophageal cancer, stomach cancer, small intestine cancer, appendix cancer, colon cancer, rectum cancer, anus cancer, liver cancer, biliary tract cancer, pancreas cancer

APPROVED BY GOVERNING BODIES:

Recommendations for the use of a given tumor marker test are based on whether there are high levels of published evidence of analytical validity and clinical utility, regardless of whether the test has been approved, cleared, or never reviewed by the FDA.

BENEFIT APPLICATION:

Coverage is subject to member’s specific benefits. Group-specific policy will supersede this policy when applicable.

ITS: Home Policy provisions apply

FEP contracts: Special benefit consideration may apply. Refer to member’s benefit plan.

CURRENT CODING:

CPT codes:

REFERENCES:

1. Abrams RA, Grochow LB, Chakravarthy A, et al. Intensified adjuvant therapy for pancreatic and periampullary adenocarcinoma: Survival results and observations regarding patterns of failure, radiotherapy dose and CA19-9 levels. Int J Radiat Oncol Biol Phys. 1999; 44(5):1039-1046.
2. Ballehaninna UK, Chamberlain RS. The clinical utility of serum CA 19-9 in the diagnosis, prognosis and management of pancreatic adenocarcinoma: An evidence based appraisal. J Gastrointest Oncol. 2012 Jun; 3(2):105-19.
3. Bast RC, Ravdin P, Hayes DF et al. 2000 update of recommendations for the use of tumor markers in breast and colorectal cancer: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 2001; 19(6):1865-78.
4. Bauer TM, El-Rayes BF, Li X, Hammad N, Philip PA, Shields AF, Zalupski MM, Bekaii-Saab T. Carbohydrate antigen 19-9 is a prognostic and predictive biomarker in patients with advanced pancreatic cancer who receive gemcitabine-containing chemotherapy: a pooled analysis of 6 prospective trials. Cancer. 2013 Jan 15; 119(2):285-92.
5. Berger AC, Garcia Jr M, Hoffman JP, et al. Postresection CA 19-9 predicts overall survival in patients with pancreatic cancer treated with adjuvant chemoradiation: A prospective validation by RTOG 9704. J Clin Oncol 2008; 26:5918-22.
6. Carmignani CP, Hampton R, Sugarbaker CE, Chang D, Sugarbaker PH. Utility of CEA and CA 19-9 tumor markers in diagnosis and prognostic assessment of mucinous epithelial cancers of the appendix. J Surg Oncol. 2004 Sep 15; 87(4):162-6.
7. Chan DW, Beveridge RA, Muss H, Fritsche HA, Hortobagyi G, Theriault R, Kiang D, Kennedy BJ, Evelegh M. Use of Truquant BR radioimmunoassay for early detection of breast cancer recurrence in patients with stage II and stage III disease. J Clin Oncol. 1997 Jun; 15(6):2322-8.
8. Cherchi PL, Dessole S, Ruiu GA, et al. The value of serum CA 125 and association CA 125/CA 19-9 in endometrial carcinoma. Eur J Gynaecol Oncol. 1999; 20(4):315-317.
9. Chu WG, Ryu DW. Clinical significance of serum CA15-3 as a prognostic parameter during follow-up periods in patients with breast cancer. Ann Surg Treat Res. 2016 Feb; 90(2):57-63.
10. Coveney EC, Geraghty JG, Sherry F, et al. The clinical value of CEA and CA 15-3 in breast cancer management. Int J Biol Markers. 1995; 10(1):35-41.
11. Dnistrian AM, Schwartz MK, Greenberg EJ, Smith CA, Schwartz DC. CA 15-3 and carcinoembryonic antigen in the clinical evaluation of breast cancer. Clin Chim Acta. 1991 Aug 30; 200(2-3):81-93.
12. Duffy MJ. Serum tumor markers in breast cancer: are they of clinical value? Clinical Chemistry 2006; 52:345-51.
13. Duffy MJ. Tumor markers in clinical practice: a review focusing on common solid cancers. Med Princ Pract. 2013; 22(1):4-11.
14. Ebeling FG, Stieber P, Untch M et al. Serum CEA and CA 15-3 as prognostic factors in primary breast cancer. Br J Cancer 2002; 86(8): 1217-22.
15. Fu Y, Li H. Assessing Clinical Significance of Serum CA15-3 and Carcinoembryonic Antigen (CEA) Levels in Breast Cancer Patients: A Meta-Analysis. Med Sci Monit. 2016 Sep 6; 22:3154-62.
16. Gion M, Boracchi P, Dittadi R et al. Prognostic role of serum CA 15.3 in 362 node-negative breast cancers. An old player for a new game. Eur J Cancer 2002; 38(9):1181-8.
17. Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, Somerfield MR, Hayes DF, Bast RC Jr; American Society of Clinical Oncology. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007 Nov 20; 25(33):5287-312.
18. Hayes DF, Bast RC, Desch CE, et al. Tumor marker utility grading system: a framework to evaluate clinical utility of tumor markers. J Natl Cancer Inst. 1996;88:1456-66
19. Hess V, Glimelius B, Grawe P, et al. CA 19-9 tumour-marker response to chemotherapy in patients with advanced pancreatic cancer enrolled in a randomized controlled trial. Lancet Oncol 2008; 9(2):132-8.
20. Hogendorf P, Skulimowski A, Durczyński A, Kumor A, Poznańska G, Oleśna A, Rut J, Strzelczyk J. A Panel of CA19-9, Ca125, and Ca15-3 as the Enhanced Test for the Differential Diagnosis of the Pancreatic Lesion. Dis Markers. 2017; 2017:8629712.
21. Huang Z, Liu F. Diagnostic value of serum carbohydrate antigen 19-9 in pancreatic cancer: a meta-analysis. Tumour Biol. 2014 Aug; 35(8):7459-65.
22. Humphris JL, Chang DK, Johns AL, Scarlett CJ, Pajic M, Jones MD, Colvin EK, Nagrial A, Chin VT, Chantrill LA, Samra JS, Gill AJ, Kench JG, Merrett ND, Das A, Musgrove EA, Sutherland RL, Biankin AV; NSW Pancreatic Cancer Network. The prognostic and predictive value of serum CA19.9 in pancreatic cancer. Ann Oncol. 2012 Jul; 23(7):1713-22.
23. Impact of follow-up testing on survival and health-related quality of life in breast cancer patients. A multicenter randomized controlled trial. The GIVIO Investigators. JAMA. 1994 May 25; 271(20):1587-92.
24. IOM (Institute of Medicine). 2011. Clinical Practice Guidelines We Can Trust. Washington, DC: The National Academies Press.
25. John AR, Haghighi KS, Taniere P, et al. Is a raised CA 19-9 level diagnostic for a cholangiocarcinoma in patients with no history of sclerosing cholangitis? Dig. Surg. 2006; 23(5-6):319-24.
26. Katz A, Hanlon A, Lanciano R et al. Prognostic value of CA 19-9 levels in patients with carcinoma of the pancreas treated with radiotherapy. Int J Radiat Oncol Biol Phys 1998; 41(2): 393-6.
27. Kau SY, Shyr YM, Su CH, et al. Diagnostic and prognostic values of CA 19-9 and CEA in periampullary cancers. J Am Coll Surg. 1999; 188(4):415-420.
28. Khatcheressian JL, Hurley P, Bantug E, Esserman LJ, Grunfeld E, Halberg F, Hantel A, Henry NL, Muss HB, Smith TJ, Vogel VG, Wolff AC, Somerfield MR, Davidson NE; American Society of Clinical Oncology. Breast cancer follow-up and management after primary treatment: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013 Mar 1; 31(7):961-5.
29. Kokko R, Holli K, Hakama M. CA 15-3 in the follow-up of localized breast cancer; a prospective study. Eur J Cancer 2002; 38(9):1189-93.
30. Kurebayashi J, Yamamoto Y, Tanaka K et al. Significance of serum carcinoembryonic antigen and CA 15-3 in monitoring advanced breast cancer patients treated with systemic therapy: a large-scale retrospective study. Breast Cancer 2003; 10(1): 38-44.
31. Levy C, Lymp J, Angulo P, Gores GJ, Larusso N, Lindor KD. The value of serum CA 19-9 in predicting cholangiocarcinomas in patients with primary sclerosing cholangitis. Dig Dis Sci. 2005 Sep; 50(9):1734-40.
32. Locker, GY, Hamilton S, Harris J et al. ASCO 2006 Update of Recommendations for the Use of Tumor Markers in Gastrointestinal Cancer. Journal of Clinical Oncology 2006; 24(33): 5313-5327.
33. Mariampillai AI, Cruz JPD, Suh J, Sivapiragasam A, Nevins K, Hindenburg AA. Cancer Antigen 72-4 for the Monitoring of Advanced Tumors of the Gastrointestinal Tract, Lung, Breast and Ovaries. Anticancer Res. 2017 Jul; 37(7):3649-3656.
34. Micke O, Bruns F, Kurowski R, et al. Predictive value of carbohydrate antigen 19-9 in pancreatic cancer treated with radiochemotherapy. Int J Radiat Oncol Biol Phys 2003; 57(1): 90-7.
35. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Esophageal and Esophagogastric junction cancers (V.3.2022), Gastric Cancer (V.2.2022), Hepatobiliary Cancers (V.2.2022), Pancreatic Adenocarcinoma (V.1.2022), Rectal Cancer (V.1.2022).
36. Ohara K, Tatsuzaki H, Molotkova NG et al. Utility of serum CA 19-9 monitoring in preoperative radiotherapy for pancreatic cancer. Hepatogastroenterology 2001; 48(39): 859-63.
37. Osayi, S., Bloomston, M., Schmidt, C., Ellison, E., & Muscarella, P. (2014). Biomarkers as predictors of recurrence following curative resection for pancreatic ductal adenocarcinoma: a review. Biomed Research International, 2014:468959.
38. Poston GJ, Tait D, O'Connell S, Bennett A, Berendse S; Guideline Development Group. Diagnosis and management of colorectal cancer: summary of NICE guidance. BMJ. 2011 Nov 9; 343:d6751.
39. Pourmadadi M, Ghaemi A, Khanizadeh A, et al. Breast cancer detection based on cancer antigen 15-3; emphasis on optical and electrochemical methods: A review. Biosens Bioelectron. 2024;260:116425.
40. Primrose JN, Perera R, Gray A, Rose P, Fuller A, Corkhill A, George S, Mant D; FACS Trial Investigators. Effect of 3 to 5 years of scheduled CEA and CT follow-up to detect recurrence of colorectal cancer: the FACS randomized clinical trial. JAMA. 2014 Jan 15; 311(3):263-70.
41. Shaikh ME, Hall S, Wen S, Liu H, Miah A, Salkeni MA. Retrospective analysis of the role of CA 15-3 as a biomarker for breast cancer relapse. Journal of Clinical Oncology May 30 2017; 35(15).
42. Shukla VK, Gurubachan, Sharma D, et al. Diagnostic value of serum CA-242, CA 19-9, CA15-3 and CA 125 in patients with carcinoma of the gallbladder. Trop Gastroenterol 2006; 27(4):160-5.
43. Sinakos E, Saenger AK, Keach J, et al. Many patients with primary sclerosing cholangitis and increased serum levels of carbohydrate antigen 19-9 do not have cholangiocarcinoma. Clin Gastroenterol Hepatol. 2011; 9(5):434-439.
44. Steinberg W. The clinical utility of the CA19-9 tumor associated antigen. Am J Gastroenterol. 1990; 85:350-355.
45. Sturgeon CM, Duffy MJ, Stenman UH, Lilja H, Brünner N, Chan DW, Babaian R, Bast RC Jr, Dowell B, Esteva FJ, Haglund C, Harbeck N, Hayes DF, Holten-Andersen M, Klee GG, Lamerz R, Looijenga LH, Molina R, Nielsen HJ, Rittenhouse H, Semjonow A, Shih IeM, Sibley P, Sölétormos G, Stephan C, Sokoll L, Hoffman BR, Diamandis EP; National Academy of Clinical Biochemistry. National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin Chem. 2008 Dec; 54(12):e11-79.
46. Wang W, Xu X, Tian B, Wang Y, Du L, Sun T, Shi Y, Zhao X, Jing J. The diagnostic value of serum tumor markers CEA, CA19-9, CA125, CA15-3, and TPS in metastatic breast cancer. Clin Chim Acta. 2017 Jul; 470:51-55.
47. Yaegashi H, Izumi K, Kadomoto S, Naito R, Makino T, Iwamoto H, Nohara T, Shigehara K, Kadono Y, Mizokami A. High Serum CA19-9 Concentration Indicates High Chemosensitivity and Better Survival in Advanced Urothelial Carcinoma. Anticancer Res. 2019 Jan; 39(1):375-380.
48. Ziske C, Schlie C, Gorschluter M et al. Prognostic value of CA 19-9 levels in patients with inoperable adenocarcinoma of the pancreas treated with gemcitabine. Br J Cancer 2003; 89(8): 1413-7.

POLICY HISTORY:

Medical Policy Group, August 2004 (2)

Medical Policy Administration Committee, August 2004

Available for comment October 5-November 18, 2004

Medical Policy Group, March 2005 (2)

Medical Policy Administration Committee, April 2005

Available for comment April 13-May 27, 2005

Medical Policy Group, July 2005 (2)

Medical Policy Administration Committee, July 2005

Available for comment July 28-September 10, 2005

Medical Policy Group, December 2006 (1)

Medical Policy Administration Committee, December 2006

Available for comment January 30-March 8, 2007

Medical Policy Group, March 2007 (2)

Medical Policy Administration Committee, March 2007

Medical Policy Group, November 2008 (2)

Medical Policy Administration Committee, April 2009

Available for comment April 1-May 15, 2009

Medical Policy Group, June 2010 (3)

Medical Policy Administration Committee July 2010

Available for comment July 2-August 16, 2010

Medical Policy Group, June 2011 (1): Updated Description, narrowed number of serum markers under Policy; policy statement unchanged, updated Key Points and References; completely removed all aspects of bladder cancer tumor markers and placed on policy 433

Medical Policy Administration Committee, August 2011

Medical Policy Group, October 2013 (1): Policy updated with literature review; clarification to policy criteria and reformatting of policy section, no change to coverage criteria; removed ICD-9 diagnosis codes; addition of pancreatic, biliary and breast cancer to Key Words

Medical Policy Administration Committee, December 2013

Medical Policy Group, June 2016: Changed Category from Medical to Laboratory

Medical Policy Group, August 2018 (9): 2018 Updated Key Points, References. No change to policy statement.

Medical Policy Group, October 2019 (9): 2019 Updates to Description, Key Points, References. Reformatted policy statement for clarity, no change to intent. Added key words: GI malignancies, gastrointestinal malignancies, gastrointestinal cancer, GI cancer, gallbladder cancer, intrahepatic biliary cancer, extrahepatic biliary cancer, esophageal cancer, stomach cancer, small intestine cancer, appendix cancer, colon cancer, rectum cancer, anus cancer, liver cancer, biliary tract cancer, pancreas cancer.

Medical Policy Group, December 2020 (9): 2020 Updates to Description, Key Points, References. No change to policy statement.

Medical Policy Group, December 2021 (9): 2021 Updates to Description, Key Points, References. Policy statement updated to remove “not medically necessary,” no change to policy intent.

Medical Policy Group, October 2022 (9): 2022 Updates to Description, Key Points, References. No change to policy statement.

Medical Policy Group, October 2023 (5): Reviewed by Consensus. Updates to Key Points; Practice Guidelines and Position Statements, and Benefit Application. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

Medical Policy Group, October 2024 (5): Reviewed by Consensus. Updates to Key Points and References. No new published peer-reviewed literature available that would alter the coverage statement in this policy.

This medical policy is not an authorization, certification, explanation of benefits, or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All medical policies are based on (i) research of current medical literature and (ii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.

This policy is intended to be used for adjudication of claims (including pre-admission certification, pre-determinations, and pre-procedure review) in Blue Cross and Blue Shield’s administration of plan contracts.

The plan does not approve or deny procedures, services, testing, or equipment for our members. Our decisions concern coverage only. The decision of whether or not to have a certain test, treatment or procedure is one made between the physician and his/her patient. The plan administers benefits based on the member’s contract and corporate medical policies. Physicians should always exercise their best medical judgment in providing the care they feel is most appropriate for their patients. Needed care should not be delayed or refused because of a coverage determination.

As a general rule, benefits are payable under health plans only in cases of medical necessity and only if services or supplies are not investigational, provided the customer group contracts have such coverage.

The following Association Technology Evaluation Criteria must be met for a service/supply to be considered for coverage:

1. The technology must have final approval from the appropriate government regulatory bodies;

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes;

3. The technology must improve the net health outcome;

4. The technology must be as beneficial as any established alternatives;

5. The improvement must be attainable outside the investigational setting.

Medical Necessity means that health care services (e.g., procedures, treatments, supplies, devices, equipment, facilities or drugs) that a physician, exercising prudent clinical judgment, would provide to a patient for the purpose of preventing, evaluating, diagnosing or treating an illness, injury or disease or its symptoms, and that are:

1. In accordance with generally accepted standards of medical practice; and

2. Clinically appropriate in terms of type, frequency, extent, site and duration and considered effective for the patient’s illness, injury or disease; and

3. Not primarily for the convenience of the patient, physician or other health care provider; and

4. Not more costly than an alternative service or sequence of services at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of that patient’s illness, injury or disease.